Discovery That Theonellasterol a Marine Sponge Sterol Is a Highly Selective FXR Antagonist That Protects against Liver Injury in Cholestasis
Figure 3
Theonellasterol reverses the effect of CDCA on the expression of canonical FXR target genes.
Relative mRNA expression of (A) OSTα, (B) BSEP, (C) SHP and (D) MRP4 in HepG2 cells treated with 10 µM CDCA alone or with the combination of CDCA plus theonellasterol 50 µM. (E) CHiP assay performed in HepG2 cells not stimulated or primed with CDCA, 10 µM, alone or in combination with theonellasterol, 50 µM. Theonellasterol antagonizes the recruitment of FXR on the MRP4 promoter. Data are the mean ± S.E. of three experiments. *P<0.05 versus cells left untreated. #P<0.05 versus CDCA alone.